Work

Single‐Cell RNA‐Seq Combined With Bulk RNA‐Seq Revealed the Involvement of Pancreatic Cancer Tissue‐Resident Macrophages in Tumour Progression and the Immunotherapy Response

Year: 2026

Type: article

Abstract: Pancreatic cancer remains a highly lethal malignancy with limited therapeutic efficacy and untapped immunotherapeutic potential, largely constrained by immune cell heterogeneity in the tumour microenvironment. Tumour-associated macrophages (TAMs), especially tissue-resident macrophages (TRMs), exert complex regulatory roles in tumour progression. Here, we integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk-seq) data from the GEO and TCGA databases to characterize macrophage heterogeneity and its functional impacts in pancreatic cancer. We delineated the tumour microenvironment landscape and identified a specific TRM subpopulation. Cell communication analysis revealed extensive interactions between TRMs and other cell types, including CXCL/MIF and notably upregulated SPP1 signalling in tumour tissues. We further established a TAM scoring system and found that clusters 4, 5, 9 and 10 were significantly associated with patient survival. Among them, TRM cluster 4 showed the highest predictive efficacy for 5-year and 10-year mortality, and effectively stratified patients into high- and low-risk groups with distinct differences in survival, immune cell infiltration and immune checkpoint expression. Importantly, TRM_C4 scores exhibited significant changes after immunotherapy, with decreased scores in responders and increased scores in non-responders. Together, our findings demonstrate the critical involvement of pancreatic cancer tissue-resident macrophages in tumour progression and immunotherapy response, and suggest that targeting specific macrophage subpopulations may represent a novel strategy to enhance immunotherapy efficacy and improve clinical outcomes for pancreatic cancer patients.

Source: Journal of Cellular and Molecular Medicine

DOI: 10.1111/jcmm.71212

Authors: Bin Wu, Chundong Hu, Fengchun Lu

Institutions: Fujian Medical University, Jiaxing University, Union Hospital

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,210